Mechanical properties that influence antimicrobial peptide activity in lipid membranes

Abstract

Antimicrobial peptides are small amphiphilic proteins found in animals and plants as essential components of the innate immune system and whose function is to control bacterial infectious activity. In order to accomplish their function, antimicrobial peptides use different mechanisms of action which have been deeply studied in view of their potential exploitation to treat antibiotic-resistant bacterial infections. One of the main mechanisms of action of these peptides is the disruption of the bacterial membrane through pore formation, which, in some cases, takes place via a monomer to oligomer cooperative transition. Previous studies have shown that lipid composition, and the presence of exogenous components, such as cholesterol in model membranes or carotenoids in bacteria, can affect the potency of distinct antimicrobial peptides. At the same time, considering the membrane as a two-dimensional material, it has been shown that membrane composition defines its mechanical properties which might be relevant in many membrane-related processes. Nevertheless, the correlation between the mechanical properties of the membrane and antimicrobial peptide potency has not been considered according to the importance it deserves. The relevance of these mechanical properties in membrane deformation due to peptide insertion is reviewed here for different types of pores in order to elucidate if indeed membrane composition affects antimicrobial peptide activity by modulation of the mechanical properties of the membrane. This would also provide a better understanding of the mechanisms used by bacteria to overcome antimicrobial peptide activity.

Effects of the antimicrobial peptide L12 against multidrug‑resistant Staphylococcus aureus

“…The variable susceptibility between gram-negative and gram-positive bacteria was likely due to structural variations in the cell wall and the cell membrane. The cell membrane is the target of the majority of AMPs (26,27). Notably, according to SEM and TEM analysis, L12 may additionally target the cell membrane.…”

Integrated microfluidic biosensing platform for simultaneous confocal microscopy and electrophysiological measurements on bilayer lipid membranes and ion channels

“…Altogether, and surprisingly, these experiments reveal that the presence of NBD‐PE has an impact on the gramicidin single channel function. As mentioned earlier, the gramicidin ion channel function can be influenced by various lipid bilayer properties (thickness, fluidity or mechanical properties) , as well as through specific peptide‐lipid interactions . Here, the lipid bilayer thickness is not altered in presence of NBD‐PE alone (Table ), and the possible influence of NBD‐PE on the fluidity cannot easily be evaluated since FRAP measurements require its presence in the lipid bilayer.…”

“…Furthermore, our platform does not allow accessing the lipid bilayer mechanical properties. PE has an inverted conical shape, which confers a negative curvature to the lipid bilayer , which in turn impacts gramicidin ion function . However, in contrast to PE, NBD‐PE has a cylindrical shape due to the presence of the bulky NBD fluorophore, so that NBD‐PE has no such effect on the lipid bilayer curvature .…”

Antibacterial activities and molecular mechanism of amino‐terminal fragments from pig nematode antimicrobial peptide CP‐1

“…[3] AMPs are small amphiphilic proteins, [4] which are found in animals and plants as essential components of the innate immune system and exert their functions to control the infectious activity of bacterial. [5] Different from antibiotics, which usually target specific steps in bacterial growth and replication, AMPs disrupt the membrane and cause the lysis of microbes through physical means. [2] In addition to their direct antibacterial activity, many AMPs have shown multiple functions, including wound healing, [6] endotoxin neutralization, [7] antifungal activity, [8] anti-biofilm activity, [9] ability to relieve septic shock, [10] and even altering the composition of the gut microbiota.…”